Author

and year

publication

Study design/

period (length

of follow-up)

Sample size/

country

(ethnicity)

Age at

diagnosis

or entry in

the screening

programme

Diabetes

type

Setting

Screening

modality/

coverage

Screening

frequency

Average disease

duration at the

first screening

round

Incidence/

prevalence

of sightthreatening

diabetic

retinopathy

Assessment

of screening

interval

Authors’

conclusion

about screening

interval

Comments

Agardh

et al.,

1993

[#23 From Echouffo 2013]

Retrospective

cohort/

5 years

[1^st 5 years after introduction of screening program]

858/Sweden

(Caucasian)

Mean age 34.9 years

for people with Type 1 diabetes/

53.8 years for people with Type 2

diabetes

Type 1

diabetes

(n = 431)

and

Type 2

diabetes

(n = 367)

Hospital based

Biomicroscopic

indirect

ophthalmoscopy with magnifying

lens and a slit

lamp through

dilated pupils/by

ophthalmologist

1–2 years if no diabetic

retinopathy or minimal

diabetic

retinopathy

19.8 years for

people with

Type 1 diabetes/

9.0 years for

people with

Type 2 diabetes

5-year incidence

of blindness in

Type 1 diabetes: 0.5% and 0.6% in

Type 2 diabetes;

5-year incidence

of moderate visual impairment

(macular oedema or proliferative

Diabetic retinopathy):

1.2% in Type 1

diabetes and

1.7% in Type 2

Diabetes

[note: most patients with loss of vision had severe retinopathy at baseline. Among those with no or mild retinopathy at baseline, loss of vision occurred in 1 Type 1 (0.2%) and 4 Type 2 (1.1%)]

No formal

testing /

implicit

Screening

interval

1 to 2 years is

appropriate

Small study size (<1000)

Note: study before year 2000 [less relevant]

Hospital based

Type 1 and 2: results reported separately

Note: most patients with loss of vision had severe retinopathy at baseline. Among those with no or mild retinopathy at baseline, loss of vision occurred in 1 Type 1 (0.2%) and 4 Type 2 (1.1%)

Kristinsson

et al.,

1995

[#24 From Echouffo 2013]

Retrospective cohort/

2 years

185/Iceland

(Caucasian)

≥ 15 years

Type 1

diabetes

(n = 87)

and

Type 2

diabetes

(n = 119)

Hospital based

Dilated

biomicroscopic

fundoscopy and

fundal photography/by ophthalmologist

Yearly

Not reported

2-year incidence

of sight-threatening diabetic

retinopathy

from no retinopathy

was 0%; 2-year incidence of any

retinopathy from

no retinopathy

was 23% in patients with

Type 1 diabetes

and 16% in those with Type 2 diabetes

No formal

testing/

implicit

2-yearly screening

for those with

Type 1 diabetes

and Type 2 diabetes without retinopathy

at diagnosis is safe.

Small study size (<1000)

Note: study before year 2000 [less relevant]

Hospital based

Type 1 and 2: results reported separately

Henricsson

et al.,

1996

[#25 From Echouffo 2013]

Retrospective

cohort/

2.9 years

1769/Sweden

(Caucasian)

30–60 years

Type 1

diabetes

(n = 370)

And Type 2 diabetes

(n = 1399)

[based on age of diagnosis < 30 years (370) and >30 years (1399)]

Population based

Colour fundal

photography

(covered fields

1–3 of the 7 standard fields,

With stereopairs

of the macula

(field 2) in eyes

Without diabetic

retinopathy; if

retinopathy, at

least two photographs were added of

standard fields

4–7)

Yearly for people

diagnosed

between 20 and 30 years of age and after 5 years of diabetes

duration; 2-yearly if

diabetes

diagnosed at ≥ 30 years of

age and until

approximately 75 years of age

18.7 years for

those aged

< 30 years and

8.3 years for those aged

≥ 30 year

Incidence of

blindness:

1.0 per 1000

person-years (95% CI 0.4–2.1);

incidence of visual impairment of 4.6 per 1000

person-years

(95% CI 3.0–6.6)

[At baseline (1^st screening) 40% ‘Type1’ and 69% ‘Type2’ had no DRP; 32 and 21% had mild DRP; 10 and 5% moderate; and 17 and 5% had severe NPDR-PDR]

No formal

assessment

of the

relationship with screening

interval /

implicit

Suggestion that a

1- year screening

interval is

effective

Small study size (<1000) for Type 1 (>1000 for Type 2)

Note: study before year 2000 [less relevant]

Note: none diagnosed before age of 30 (‘Type1’) went blind; in >30 group (‘Type2’), incidence blindness was 1.3 per 1000; incidence of moderate visual impairment was 3.4 per 1000 (<30 y group) and 5.0 (>30 y group)

Note: Multivar analysis showed statist sign assoc between blindness / visual impairment and old age, long duration of diabetes, and poor glycaemic control; HbA1c highest quartile, (>= 8.5%), associated with 65% increase in risk (95% confidence interval 14-130%).

Ling et al.,

2002

[#31 From Echouffo 2013]

Retrospective

cohort/

6 years

775/England

(mostly

Caucasian)

[Note: ‘rural population’]

15–99 years [mean age 72.1]

Type 1

diabetes

(n = 104)

and

Type 2

diabetes

(n = 671)

Population based

(primary

care)

Non-mydriatic

fundus single-field photography and indirect

ophthalmoscopy

2-yearly

13 years

2-year incidence

of non-proliferative

diabetic retinopathy

2.20% at round

2 of screening

and 2.25 at round 3; 2-year incidence

of clinically

significant

maculopathy

4.8% at round

2 of screening

and 5.2% at

round 3

(including

patients with previously known and newly diagnosed

retinopathy)

[Baseline prevalence: background retinopathy (21.4%), proliferative (2.8%), clinically significant macular oedema: (6.1%)]

Implicit

assessment

screening

interval:

incidence

of sight-threatening

diabetic

retinopathy

appears to

be stable

over rounds

of screening

in a 2-yearly

strategy

No reason to

believe that a

2-year screening

interval would

be detrimental

Small study size (<1000)

Type 1 and 2: not analyzed separately; majority is Type 2

Rural population

No differentiation between patients without DRP and those with mild DRP at baseline

Hansson-

Lundblad

et al.,

2002

[#26 From Echouffo 2013]

Retrospective

cohort/

8 years

264/Sweden

(Caucasian)

≥ 30 years

Type 1

diabetes

(n = 39)

and

Type 2

diabetes

(n = 225)

Population based

(primary

care)

Mydriatic 3-field fundal

photography or

biomicroscopy

1–2 years if no or mild diabetic

retinopathy

Not reported

8-year rate of

blindness in

Type 1 diabetes

was 0% and 2% for Type 2 diabetes [= 3 patients]

[includes patients with no DRP and with mild DRP at baseline]

No formal

testing/

implicit

A 2 year screening

regimen may

be appropriate

Small study size (<1000)

Type 1 and 2: analyzed separately; majority is Type 2; small number of Type 1 patients

Note: includes patients with no DRP and with mild DRP at baseline

Younis

et al.,

2003

[#27 From Echouffo 2013]

Retrospective

cohort/

6 years of

follow-up

501/England

(96.2%

Caucasian)

< 30 years

Type 1

diabetes

Population based

(primary

care)

Non-stereoscopic

3-field mydriatic

photography (and modified

Wisconsin

grading)

Yearly for

patients with non-sightthreatening diabetic

retinopathy (no

retinopathy or background

retinopathy)

3.0 years

Cumulative

incidence of

sight-threatening

diabetic retinopathy in

patients without baseline

retinopathy was

0.3% (95% CI 0.0–0.9) at 1 year and 3.9% (1.4–5.4) at

5 years; Rates of

progression to

sight-threatening

diabetic retinopathy in

patients with

background and

mild pre-proliferative

diabetic

retinopathy at

1 year were

3.6% (0.5–6.6)

and 13.5% (4.2–22.7), respectively

For a 95%

likelihood of

remaining

free of sight-threatening

diabetic retinopathy,

mean

screening

intervals by

baseline

status were:

no

retinopathy

5.7 (95% CI 3.5–7.6)

years; background

retinopathy

1.3 (95% CI 0.4–2.0)

years; and

mild preproliferative diabetic

retinopathy

0.4 (95% CI 0–0.8) years

Screening at 2- to

3-year intervals,

rather than annually, for patients without retinopathy at

diagnosis

Small study size (<1000)

Type 1 only

Younis

et al.,

2003

[#17 From Echouffo 2013]

Retrospective

cohort/

3.5 years of

follow-up

4770 patients/

England

(vast majority

Caucasian)

> 30 years

Type 2

diabetes

Population based

(primary

care)

Non-stereoscopic

mydriatic 3-field photography/

graded by trained graders

Yearly for patients

with non-sightthreatening

diabetic

retinopathy (no diabetic

retinopathy or background

retinopathy)

7.8 years

Yearly incidence

sight-threatening

diabetic retinopathy in

patients without

retinopathy at

baseline was 0.3% (95%

CI 0.1–0.5) in

the first year,

rising to 1.8%

(95% CI 1.2–2.5) in the fifth year;

Cumulative 5-year incidence

was 3.9% (95%

CI 2.8–5.0)

For a 95%

probability

of remaining

free of sight-threatening

diabetic

retinopathy,

mean

screening

intervals by

baseline status were: no retinopathy

5.4 years

(95% CI 4.7–6.3), background

1.0 year (95% CI 0.7–1.3) and mild preproliferative diabetic

retinopathy

0.3 years (95% CI 0.2–0.5)

A 3-year screening

interval could be

safely adopted

for patients with no

retinopathy

Type 2 only

Maguire

et al.,

2005

[#28 From Echouffo 2013]

Retrospective

cohort/

12 years

668/Australia

(not reported)

Children and

adolescents

Type 1

diabetes

Hospital based

Seven-field

stereoscopic

mydriatic fundal

photography/

graded by an

ophthalmologist

Yearly

Not reported

Not reported

Significant

increase in

retinopathy

after 2 years

from the first

eye exam

(P = 0.03) in

age group

> 11 years,

but not until

6 years (P = 0.01) in the

age group

< 11 years

[Prevalence retinopathy

at baseline screening 16% in young (<11 year group) and 22% in older (>11 year group). Overall, 136 of 668 had retinopathy at baseline]

No risk of missing clinically significant, vision threatening or treatment requiring

retinopathy by extending screening interval to 2 years

Small study size (<1000)

Note: study on children and adolescents

Note: includes patients with no DRP and with mild DRP at baseline

Hospital based

Type 1 diabetes only

Note: Prevalence retinopathy

at baseline screening 16% in young (<11 year group) and 22% in older (>11 year group). Overall, 136 of 668 had retinopathy at baseline; 1-2 years later, in <11 group, retinopathy

regressed in 80% but progressed in none. In >11 group retinopathy

regressed in 36% and progressed in 13%

Olafsdottir

et al.,

2007

#19 [From Echouffo 2013]

Retrospective

cohort/

10 years

296/Caucasian

16–90 years

Type 1

diabetes

(n = 97),

Type 2

diabetes

(n = 199)

Population based

Dilated slit-lamp ophthalmoscopy and colour

fundus photo

graphy/by an

ophthalmologist using. worst eye to define retinopathy level

2-yearly if no

retinopathy and

yearly once

development of [mild] retinopathy

18 years

No patient went

from no retinopathy to

sight-threatening

retinopathy in

less than 2 years’

[172/296 did not

develop DR during 10-year observation

period; 96/296 developed mild NPDR; 6 clinically significant diabetic macular oedema; 23 preproliferative DR; 4 PDR]

No formal

testing/implicit

Every 2 years

Small study size (<1000)

Type 1 and 2: analyzed separately; majority Type 2

Note: all patients developing macular oedema or PDR in 10 year period had already been diagnosed as having mild NPDR and entered annual screening protocol before STDR developed. ‘No patient had any undue delay in treatment’

Misra

et al.,

2009

[#29 From Echouffo 2013]

Retrospective

cohort/

17 years

20 788/UK

(mainly

Caucasian)

Mean age:

68.8 years

Type 1

diabetes

(n = 205)

and

Type 2

diabetes

(n = 20,583)

Population based

Mydriatic 2-field fundus photography/ graded by a diabetologist and an opththalmologist

17–19 months

[‘invited yearly’; except those with

More severe NPDR who were re-screened at 6 months]

6.8 years

91% decrease in

the prevalence

of sight-threatening

diabetic retinopathy from

the first round of

screening (1.7%)

to the last round 17 years later (0.16% in year 2006)

Compared with intervals of 12–18 months, intervals of

19–24 months

were not

associated with a higher risk of either referable

or sight-threatening

diabetic

retinopathy

(odds ratio 0.93, 95%

CI 0.82–1.05), but interval of

more than

24 months

associated with an increase risk

of diabetic

retinopathy

(odds ratio

1.56, 95% CI 1.14–1.75)

Screening intervals

of 18 months– 2 years can be safe for patients at low risk

Small study size (<1000) for Type 1 (>1000 for Type 2)

Type 1 and 2: not analyzed separately; vast majority is Type 2

Note: includes patients with no DRP and with mild DRP at baseline

Note: not clear what causes the differences between screening intervals (non-compliance?); high risk of confounding

Note: of 6307 patients whose diabetes was first diagnosed at age 40 years or older, with no retinopathy or maculopathy at their first screen, followed for at least 2 years and with a second screen within 2 years of the first, no patients were found to have referable retinopathy within 2 years of the first screen.

Note: decline in STDR during 17 years of screening possibly explained by improved management of risk factors (glycaemic

Control; hypertension), and earlier entry of patients into screening programmes as a result of improved detection and referral by GPs. [and results of the screening itself: referral of high-risk patients]

Arun et al.,

2009

[#44 From Echouffo 2013]

Retrospective

cohort

study/

5 years

6430/England (mainly

Caucasian)

[6,430 = population estimated to be at risk for vision loss from diabetic retinopathy]

16–64 years

Type 1

diabetes

(n = 5)

and

Type 2

diabetes

(n = 15)

[numbers refer to patients with partial or complete loss of vision]

Population based/

relied on

blindness

register

Mydriatic fundus

photography/

by trained

screeners

Assumed to be 1 year

Not reported

Annual incidence

of blindness: 0.22

per 1000, and of

partial sightedness

0.43 per 1000 patients with diabetes

No formal

testing of

relation to

screening

interval/implicit

In a district that has operated retinal screening since 1986, diabetic retinopathy was not the commonest cause of blindness in the working age population, consistent with an effect of systematic annual screening

Type 1 and 2

Based on blindness registry and estimation of the size of the population at risk

Soto-Pedre

et al.,

2009

[#30 From Echouffo 2013]

Retrospective

cohort/

6 years

430/Spain

(mainly

Caucasian)

Mean age

52.7 years

Type 1

diabetes

(n = 320)

and

Type 2

diabetes

(n = 110)

[Type1 defined as <30 years of age and

receiving insulin]

Hospital based

(tertiary

care)

45º non-mydriatic

single-field fundus

photography

(centred on the

macula and one

photo for each

eye)

Not reported

10.1 years for

those with no

diabetic

retinopathy at

first screen and

14.9 years for

those with

diabetic

retinopathy at

first screening

If no diabetic

retinopathy at

baseline, the

probability of

remaining free of

STDR was

97% (95% CI 94–99%) at the end of the fourth year. If mild NDRP at baseline, the probability of

remaining free of STDR was 99% (95%CI 95–100%) at end of first year of follow-up and 94% (95% CI 88–97%) at end of second year

Interval for at least a 95% estimated

probability of

remaining free of STDR

for no baseline

DRP was 4 years for those who had Type 1 diabetes

and 3 years for those who had Type 2 diabetes.

For patients

with mild NPDR at baseline, the interval for at least a 95% probability of

STDR free survival

was 1 year, or in those with a level of glycated

haemoglobin

≤ 7.5%.

Screening at a

3–4 year interval

for patients with

diabetes patients

of diabetic

retinopathy is safe

because of their

low risk of

developing sightthreatening

diabetic retinopathy.

Patients with mild

non-proliferative

diabetic retinopathy

require screening

at a 1-year interval,

or at a 2-year interval with good

metabolic control

Small study size (<1000)

Hospital based

Type 1 and 2: analyzed separately

Note: the screening interval that could be safely adopted for patients with DM for early detection of STDR (safe screening interval) was defined as the interval for an estimated probability of at least 95% of remaining free of STDR (in agreement with the proposal of Younis and colleagues)

Agardh

and

Tababat-

Khani,

2011

[#32 From Echouffo 2013]

Prospective

Cohort

3 years

1322/Sweden

(Caucasian)

Mean age

55 years

(SD 12) at diagnosis; 60 years at baseline

Type 2

diabetes

Population based

Fundal

photography

(images—1 central

and 1 nasal fields)

3-year screening

interval if no diabetic

retinopathy at baseline

[in study cohort all patients had no DRP at baseline]

6 years

From no DRP at baseline: after 3 years, 73% still had no DRP, 28% had mild or moderate DRP, 0% had severe NPDR or PDR

73% of patients

without

retinopathy and 28% with mild or moderate

diabetic

retinopathy

after 3 years

3-year screening

intervals is safe

in subjects with

mild Type 2 diabetes and no

diabetic retinopathy

Type 2 only

Jones

et al.,

2012

[#33 From Echouffo 2013]

Prospective cohort

Upto 17 years

20 686/

England

(mainly

Caucasian)

Median 66.7

(IQR 58.0–74.5) for those

without retinopathy; 68.0 (IQR 58.5–75.7) for those with non-proliferative diabetic

retinopathy, 66.3 (IQR

55.7–66.3) for those

With proliferative diabetic retinopathy

Type 2

diabetes

Population based

Fundal

photography

(two images of

each eye)

Assumed to be 1-year interval

(but variable

interval, up to 24 months after baseline

examination)

Not reported

(range 0–10 years)

5-year incidence

among patients

without diabetic

retinopathy at

baseline was 4.0% for pre-proliferative

diabetic retinopathy,

0.59% for sight-threatening

maculopathy, 0.68% for proliferative

diabetic retinopathy;

the respective 10-year incidences

were 16.4, 1.2 and 1.5%, respectively.

Among those with non-proliferative

Diabetic retinopathy

at baseline, after

1 year 23%

developed preproliferative

diabetic

retinopathy, 5.2%

developed

maculopathy and

6.1% developed

proliferative diabetic

retinopathy; the

respective 10-year incidences were 53, 9.6 and 11%, respectively

No formal

testing of the

relationship

between

screening

interval and

incidence of

various stages

of diabetic

retinopathy/

implicit

Few patients

without diabetic

retinopathy at first

screen developed

pre-proliferative

diabetic retinopathy,

proliferative

diabetic retinopathy or sight-threatening

maculopathy after 5–10 years of follow-up. Screening intervals longer than 1 year may be appropriate for people without

diabetic retinopathy

at diagnosis

Type 2 only

Thomas

et al.,

2012

[#34 From Echouffo 2013]

Retrospective

Cohort

4 years

57 199 (with

no evidence

of diabetic

retinopathy

at baseline)/

Wales (mainly

Caucasian)

≥ 30 years

Type 2

diabetes

Population based

Fundal

photography

≥ 1 year

3.9 years for

those with no

retinopathy

and 5.1 years

among those

with diabetic

retinopathy

From no DRP at baseline: 4-year incidence of any and referable diabetic retinopathy: 360.27 and 11.64

per 1000, resp.

For those on insulin treatment and with diabetes duration ≥ 10 years, incidence

of referable diabetic retinopathy at 1 and 4 years was 9.61 and 30.99 per 1000, resp

No formal

testing of the

relationship

between

screening

interval and

incidence of

various stages of diabetic

retinopathy/

implicit

Extension of the

screening interval

for people with

Type 2 diabetes

without diabetic

retinopathy beyond 12 months, with the

possible exception

of those with

diabetes duration

≥ 10 years and on insulin

Type 2 only

Forster 2013a

Retrospective cohort/ 4 years

32,340/UK (mainly Caucasian = 44%; Carribean 16%; African 13%)

>12 years

65-74 years (24.6%)

Type 2 diabetes (32,340)

Population based (primary care)

South East London diabetic eye

screening service

fourth (46.2%) or fifth (42.8%)

most deprived quintile

screening service based in deprived and ethnically

heterogeneous south London boroughs: may not be representative

of English screening population

Non-mydriatic

fundus photography with 45 deg angle (dilated pupils; in color); graded according to NHS specifications by qualified graders

STDR = moderate or

severe nonprolif (R2), prolif retinop

(R3), or referable maculopathy (M1) [patients with STDR are referred to ophthalmology]

Yearly (‘invited for annual screening’)

Differs per screening year:

% with <1 year

2008: 18.7%

2009: 34.9%

2010: 39.9%

2011: 48.6%

Note: annual diabetic eye screening implemented in England since 2008, i.e. 1^st 4 years of screening analyzed

Patients with mild (nonprolif) retinopathy at 1^st screen: STDR at 2^nd or later screen declined from 21.6% (2008) to 8.4% (2011)

Patients w/o retinopathy at 1^st screen: STDR at 2^nd or later screen declined from 9.2% (2008) to 3.2% (2011)

No formal

testing/

implicit

After the inception of population-based diabetic eye screening, patients at lower risk of STDR contribute an increasing proportion to the eligible population, and the proportion

detected with STDR at second or subsequent screening rounds declines rapidly

Findings provide further support to argument for less frequent monitoring of patients who do not have retinopathy detected at screening.

Type 2 only

Decrease in STDR

attending a second or later screen most likely attributed to patients with existing STDR having been identified at screening and removed from

the eligible population, with lower-risk

patients contributing a larger fraction of

the eligible population for subsequent

screening rounds. [improved treatment (BP; glucose) may also contribute]

Note: findings reflect

changes in incidence in screening population

rather than resident population.

Note: proportion with duration of diabetes of <1 year at first screen increased from 18.7% in 2008 to 48.6% in 2011.

Note: Over study period, 96.5% of

patients invited for screening had attended

at least once.

Forster 2013b

Retrospective cohort/ 4 years

[based on data from same cohort as in Forster 2013a]

6,556/UK

(mainly Caucasian = 47%; Caribbean 18%; African 13%)

PS. in final analysis 2,086 excluded mainly because of only attending 1^st screen >> 4,470 patients in analytic sample

Cf. Forster 2013a, analysis is limited to participants who first attended for screening in 2008

>12 years

65-74 years (23.4%)

Type 2 diabetes (92.4%)

[rest=type 1 or unknown type]

Population based (primary care)

South East London diabetic eye

screening service

fourth (45.8%) or fifth (42.2%)

most deprived quintile

screening service based in deprived and ethnically

heterogeneous south London boroughs: may not be representative

of English screening population

Non-mydriatic

fundus photography with 45 deg angle (dilated pupils; in color); graded according to NHS specifications by qualified graders

STDR = moderate or

severe nonprolif (R2), prolif retinop

(R3), or referable maculopathy (M1) [patients with STDR are referred to ophthalmology]

Yearly (‘invited for annual screening’)

67.0% diagnosed with diabetes for <5 years

Note: annual diabetic eye screening implemented in England since 2008, i.e. 1^st 4 years of screening analyzed

Patients who do not attend screening are at increased risk of STDR. Tracing of non-attenders with evidence of established retinopathy

should be an important fail-safe procedure.

STDR at screening

OR adjusted for dur diab, age, sex, depriv index, year screen, diab type;

ref = screened each year

All participants

Not attend 1 y

1.31 [0.88; 1.94]

Not attend 2 yrs

3.76 [2.14; 6.61]

No retin 1^st scrn

Not attend 1 y

1.24 [0.67; 2.29]

Not attend 2 yrs

4.34 [1.94; 9.71]

Mild retin 1^st scrn Not attend 1 y

1.46 [0.86; 2.48]

Not attend 2 yrs

2.94 [1.29; 6.72]

No formal

testing/

implicit

[does not provide useful information on screening interval required]

Stresses importance for tackling non-attendance

Type 1 and 2: not analyzed separately; vast majority is Type 2

Increasing duration of diabetes (p<0.001), greater deprivation (p=0.001) and type 1 diabetes (p<0.001) were each associated with higher rates of missed screening. Missing screening was not associated with sex, but was more frequent in early adult years.

From literature: patients who do not

attend screening have poorer HbA1c and blood pressure

control and have been diagnosed with diabetes for longer

Note: 79% individuals

invited for screening in England attended in 2010/2011

Looker 2012

Cross-sectional study

51,526/UK

[Note: period overlaps with the start of the screening programme]

>12 years

Mean age at diagnosis 61.8 yrs

Newly diagnosed type 2 diabetes

All patients registered with type 2 diabetes Jan 2005 – May 2008

Population based

Scottish

clinical database covers

around 99% of diabetic population

Screen programme (DRS) nation-wide since 2007

single-field digital photograph, with mydriasis if required; slit-lamp examination if required; centralised grading

eye is given a retinopathy and maculopathy grade (R0, R1, R3, R4, M1, M2)

Not relevant: only results on first screening presented = prevelance

Newly diagnosed type 2 diabetes;

median time to screening:

Overall i.e. 2005-2008:

315 days

Diagn in 2008:

83 days

Prevelance at first screen (31 dec 2010 91% had attended a screening)

All patients:

Any retinopathy

19.3%

Referrable retino

1.9%

Patients first screened after > 1 year:

Any retinopathy

20.5%

Referrable retino

2.3%

53.8% screened within 1 year diagnosis

Not applicable [only prevelance at 1^st screening is reported; no follow-up]

[does not provide direct information on screening interval required]

Prevalence of retinopathy at

first screening is lower than in previous UK studies, consistent

with earlier diagnosis of diabetes. Most newly diagnosed

type 2 diabetic patients in Scotland are screened

within acceptable interval and the prevalence of referable disease is low, even in those with delayed screening.

Data suggest that a delay in diagnosis

of up to 2 years would have a minimal impact on prevalence

of STDR

Type 2 only

Any retinopathy

at screening was associated with male sex (OR 1.19, 95% CI

1.14, 1.25), HbA1c (OR 1.07, 95% CI 1.06, 1.08 per 1% [11 mmol/mol] increase), systolic BP (OR 1.06, 95% CI 1.05, 1.08 per 10 mmHg increase), time to screening (OR

for screening >1 year post diagnosis01.12, 95% CI 1.07, 1.17) and obesity (OR 0.87, 95% CI 0.82, 0.93) in multivariate

analysis.

Note: ‘diabetic retinopathy’ also

occurs in non-diabetic populations ranging from 5-8%; suggests that even with moves to minimise delay in diagnosis of diabetes

through diabetes screening programmes we would not

anticipate achieving a prevalence of diabetic retinopathy at

the time of diagnosis of less than 5%.

Looker 2014

Retrospective cohort/

5 years

182,397/UK

[Note: study reports yield of referable disease

for the first 5 years of the DRS programme]

> 12 years

Mean age at 1^st screen

64 yrs [54;73]

Diabetes duration at 1^st screen 5.7 yrs [2.4;10.8]

Type 2 diabetes

161,135 (88%)

Type 1 diabetes 20,521 (11%)

Diagnosis before 31 May 2008

Population based

Scottish

clinical database covers

around 99% of diabetic population

Screen programme (DRS) nation-wide since 2007

Patients with diagnosis diabetes before 31 May 2008 and >= 1 successful DRS examination

single-field digital photograph, with mydriasis if required; slit-lamp examination if required; centralised grading

eye is given a retinopathy and maculopathy grade (R0, R1, R2, R3, R4, M1, M2)

R3, R4, M2 trigger reverral to specialist eye clinic

Yearly (‘invited for annual screening’)

All patients

5.7 yrs [2.4;10.8]

Yield referable eye disease was highest in the first 2 years of

screening (7.0% and 6.0%) before stabilising at ∼4.3%.

Majority of referrals due to maculopathy with 73% of referrals in 2010 based on a finding of

maculopathy.

Referrable eye dis

All patients

2006: 7.0%

2007: 6.0 %

2008: 4.3%

2009: 4.3%

2010: 4.3%

Type 1 patients

2006: 14.8%

2007: 12.9 %

2008: 10.3%

2009: 10.8%

2010: 11.0%

Type 2 patients

2006: 5.9%

2007: 5.1 %

2008: 3.6%

2009: 3.6%

2010: 3.6%

No formal

testing/

implicit

[does not provide direct information on screening interval required]

Referral rates

for retinopathy have stabilised at relatively

low rates

Type 1 and 2: analyzed separately

The commonest cause for referral is for

suspected macular oedema (maculopathy).

Those with referable disease were more often male, with

longer DM duration, higher HbA1c, and higher systolic blood

pressure. Additionally, for people with T1DM, referable disease

was also associated with older age, higher BMI, higher diastolic

blood pressure and higher prevalence of smoking. By contrast,

in T2DM, referable disease was also associated with lower

prevalence of smoking, lower BMI and greater use of insulin

therapy.

Note: higher risk for referrable disease in T1DM vs T2DM (OR=3.08 [2.89;3.28]) mediated principally via DM duration (about twice greater in T1DM)

Papavasileiou 2014

retrospective cohort/ 2 year

Not stated/ UK

Not stated [study based on DRS data 2010-2012 from Wirral, UK]

Mainly type 2 (not specified)

Population based

DRS programme UK

Mydriatic 2-field digital photography by trained graders

Yearly

Not stated

Referable retinopathy decreased from 5.6% for 2010–2011 to 4.94% during the same period in 2011–2012. The incidence of proliferative retinopathy (R3) dropped from

0.7% last year to 0.52% this year.

No formal

testing/

implicit

[does not provide direct information on screening interval required]

Referral rates

for retinopathy have stabilised at relatively

low rates

Study size not stated but probably >1000

Type 1 and 2: not analyzed separately; majority Type 2

This short paper can not be judged due to a lack in necessary details

Porta 2013

retrospective analysis/ 20 years

[prospective data collection]

4,320/Italy

Mainly Caucasian

Patients were stratified according to age < or > 30 yrs, insulin use:

OO-NIT

Older onset not insulin treated (2,934; age 62; diab duration 5.9 yrs)

OO-IT

Older onset insulin treated (689; 58; 8.5)

YO-IT

Younger onset insulin treated 671; 22; 8.8)

YO-NIT

Younger onset not insulin treated (26; 39; 16.1) [this group was too small and not analysed]

Type 1 diabetes and

Type 2 diabetes

[not specified, but see categories based on age and insulin use]

Population based

Diabetic Retinopathy Centre screening outpatients;

main teaching hospital Turin

prospect collected data 1991-2010

Until 2000

by direct and indirect ophthalmoscopy; after 2000, nonmydriatic

digital fundus photography; Grading by diabetes specialists after training

mild non-proliferative retinopathy not requiring

referral (ETDRS level ≤35)

were given re-screening appointments.

moderate

non-prolif retinopathy requiring referral or worse (pre-proliferative,

proliferative, photocoagulated DR, advanced diabetic eye disease with or without macular involvement) referred to ophthalmologist

Variable

Patients were stratified (OO versus YO) according to duration of diabetes < or > 10 years

In patients without DRP at baseline:

6 year cumululative incidence referable retinopathy

10.5% (95% CI 9.4, 11.8). Retinopathy progressed

within 3 years to referable severity in 6.9% (95% CI 4.3, 11.0) of patients with age at onset ≥30 years, who were on insulin treatment and had a known disease duration of 10 years or longer.

The other patients, especially those with age at onset <30 years, on insulin and <10 years duration, progressed more slowly.

Average months needed for 5% patients to develop referable retinopathy (from no DRP):

56 (95% CI 49, 64) for OO-NIT with <10 yrs diab duration, 33 (95% CI 23, 51) for OO-NIT with ≥10 yrs duration, 41 (95% CI 24, 57) for OO-IT with <10 yrs duration, 27 (95% CI 15, 38) for OO-IT ≥10 yrs duration, 60 (95% CI 45, 79) for YO-IT <10 yrs duration and 39 (22, 51 95%CI) for YO-IT ≥10 yrs duration

No formal

testing/

implicit

None of the subgroups reached 5% cumulative incidence of referable retinopathy within 2 years of a negative screening.

Screening can be repeated safely

at 2 year intervals in any patient without retinopathy. Longer

intervals may be practicable, provided all efforts are made to ensure adherence to standards in procedures and to trace and recall non-attenders.

Small study size (<1000) for 3 out of 4 subgroups including Type 1 (OO-NIT = older onset not insulin treated has >1000)

Type 1 and 2: not analyzed separately (although age/insulin-use are categorized)

Knowledge of diabetes duration and type of glucose-lowering treatment may suffice to guide re-screening appointments: 2-year intervals are safe in any patient with type 1 or 2 diabetes and no retinopathy; patients with a shorter duration of diabetes can potentially be seen even less frequently (e.g. at 3-year intervals)

Scanlon 2013

Retrospective cohort/

4 years

19,044/UK

(predominantly white Caucasian)

[English NHS Diabetic Eye Screening Programme; Gloucestershire]

2005 – 2010: patients screened at least twice

> 12 years

median age at 1^st screen

66 yrs [57;74]

Not stated [majority type 2]

Population based [primary care]

English NHS Diab Eye Screen Prog - Gloucestershire: mobile screening

programme in 85 primary care practices

People screened at least twice between 2005-2010 and with no DR (R0), or background DR in 1 eye (R1a) or in both eyes (R1b) included in study sample

Two field 45^o digital retinal

images (macular and disc centred)

graded in central office by experienced

quality assured team

eye is given a retinopathy + maculopathy grade (R0, R1, R2, R3, R4, M0, M1)

R1a=R1 1 eye

R1b=R1 2 eyes

R2, R3, M1 trigger referral to specialist eye clinic

Yearly (‘invited for annual screening’)

Median 13.5 m [12;15]

Patients with mild background

Retinop (R1) managed

as R0: receive annual screening

Not stated

Risk of progression [to referable retinopathy] is significantly higher for those with background

DR in both eyes than those with background retinopathy in only one or in

neither eye.

Median followup

41 m [24;53]

Progression during followup (~ 4 years):

R0 at baseline

N=12,491

To RDR

3.2%

HR=1 (ref)

To M1

2.9%

HR=1 (ref)

To R3

0.07%

HR=1 (ref)

R1a at baseline

N=3,744

To RDR

8.3%

HR=2.9 [2.5;3.3]

To M1

7.1%

HR=2.6 [2.3;3.1]

To R3

0.11%

HR=1.6 [0.5;5.0]

R1b at baseline

N=2,809

To RDR

28.2%

HR=11.3 [10.0;12.8]

To M1

21.8%

HR=9.1 [7.9;10.4]

To R3

1.07%

HR= 14.9 [7.1;31.5]

No formal

testing/

implicit

The cumulative 4-year risk of progression

to proliferative DR is less than one in 1000 for those with no DR or in 1 eye only but was found in one in 200 of those with background

DR in both eyes. Similarly, the cumulative 4-year risk of development of referable DR was 1 in 3 for those with

background DR in both eyes but less

than 1 in 10 and 1 in 20 in those with only one or neither eye affected.

‘there is a strong

argument for optimizing screening

intervals based on individual risk. This

risk may be based on a previous screening

result or on the basis of previously defined individual risk factors’

Type 1 and 2: not analyzed separately; majority Type 2

A total of 8.3% of those with R1a and 28.2% of those with R1b progressed to any RDR, hazard ratios 2.9 [2.5–3.3] and 11.3 [10.0–12.8]. Similarly 7.1% and 0.11% of those with R1a progressed to M1 and R3, hazard ratios 2.7 [2.3–3.2] and 1.6 [0.5–5.0], compared to 21.8% and 1.07% of those with R1b, hazard ratio 9.1 [7.8–10.4] and 15.0 [7.1–31.5]

By age group (10-year age groups): within each age group, HR for progression in group 1b (R1 in both eyes) and 1a (R1 in one eye) statistically significant

(respectively p < 0.001, and p < 0.01)

Note: likely that confounding factors are present, those with background DR are

likely to have higher levels of HbA1c and to have had diabetes for longer. These data were not included as they are not routinely available in screening programmes.

Note: rate progression of diabetic retinopathy has slowed in more recent time periods. This may reflect earlier

diagnosis of Type 2 diabetes, improved control of hyperglycaemia and treatment of hypertension in Type

1 and Type 2 diabetes

Stratton 2013

Retrospective cohort/

4 years

[1^st + 2^nd baseline screen + median 2.8 years followup]

14,554/UK

(predominantly white Caucasian)

[English NHS Diabetic Eye Screening Programme; Gloucestershire]

2005 – 2010: patients screened at least three times [cf. Scanlon 2013]

> 12 years

median age at 1^st screen

65 yrs [56;73]

Not stated [majority type 2]

Population based [primary care]

English NHS Diab Eye Screen Prog - Gloucestershire [see Scanlon 2013]

patients showing

either no DR (R0M0) or only mild NPDR

(R1M0) in one or both eyes at 2

consecutive annual screenings (: ‘baseline screenings’) and in whom there

was at least one further follow-up screening

episode

Two field 45^o digital retinal

images (macular and disc centred)

graded in central office by experienced

quality assured team

eye is given a retinopathy + maculopathy grade (R0, R1, R2, R3, R4, M0, M1)

STDR defined as R2, R3, and/or M1

Yearly (‘invited for annual screening’)

Median 13.5 m [12;15] between the 2 baseline screenings

Patients with mild background

Retinop (R1) managed

as R0: receive annual screening

Not stated

Risk of progression to STDR is significantly higher for those with background

DR in two consecutive screens

Median followup

2.8 y [1.3;3.3] after the two ‘baseline screenings’

Progression to STDR during followup (~ 2.8 years):

R0R0/R0R0

N=7,246

To STDR

120

HR=1 (ref)

R1R0/R0R0

1,266

To STDR

30

HR=1.5 [1.0;2.3]

R1R1/R0R0

343

To STDR

12

HR=2.6 [1.4;4.7]

R0R0/R1R1

1,778

To STDR

80

HR=2.9 [2.2;3.8]

R1R0/R1R0

897

To STDR

49

HR=3.6 [2.6;5.1]

R1R1/R1R0

356

To STDR

23

HR=4.8 [3.0;7.4]

R0R0/R1R1

853

To STDR

82

HR=6.0 [4.5;7.9]

R1R0/R1R1

656

To STDR

108

HR=10.0 [7.7;13.0]

R1R1/R1R1

1,159

To STDR

299

HR=18.2 [14.7;22.5]

No formal

testing/

implicit

Model used to predict proportion referable DR (STDR) from time of 2^nd nonreferable screening episode:

by 1/2/3/5/10 years

R0R0/R0R0

0.7% (1 year)

1.2

1.9

3.0

5.9 (10 years)

R1R0/R0R0

1.0%

1.9

2.8

4.5

8.6

R1R1/R0R0

1.5%

3.0

4.4

7.1

13.2

R0R0/R1R1

1.8%

3.5

5.1

8.2

15.2

R1R0/R1R0

2.2%

4.4

6.4

10.1

18.3

R1R1/R1R0

2.8%

5.5

8.0

12.7

22.4

R0R0/R1R1

3.8%

7.3

10.6

16.4

28.1

R1R0/R1R1

6.7%

12.4

17.5

26.1

41.2

R1R1/R1R1

12.0%

21.4

29.0

40.4

57.5

Combining results from 2 consecutive years of photographic screening enables estimation of the risk of future development of STDR

‘In countries with systematic

screening programs, these results could inform decisions about screening frequency’

Type 1 and 2: not analyzed separately; majority Type 2

‘estimating risk in this way can be useful in countries with systematic screening programs, to develop screening models to

allocate limited monies more efficiently by varying the screening intervals depending

on an individual’s identified risk’; ‘risk estimator essentially helps remove the requirement for complex clinical-based data, as even if none of these are taken into account, we can differentiate risk by 18:1’

Note: authors state that further modelling is required for explicit recommendations of the screening frequencies; also ‘to be generalizable, the results would need to be validated in other populations’

Note: average attendance following

invitation was 74% in any one year

Leese 2015

Retrospective cohorts/multicentre/ 4 years

[1^st + 2^nd baseline screen + 1.6-3.3 years followup]

7 diab

retinal screening programs across U.K. / between

2005-2012

354,549/UK

(predominantly white Caucasian)

7 diab

retinal screening programs across U.K. / between

2005-2012;

patients screened at least three times

study size varies

19,358 – 138,077 patients

> 12 years

median age at 1^st screen varied from

61-64 years (38–48% <60)

Majority Type 2 diabetes

6–10% Type 1

diabetes

Population based [primary care]

7 UK programs: 3 whole nation programs

in Wales, Scotland, Northern

Ireland + 4 English

regional programs(BrightonDerbyshire, Leeds, Staffordshire)

patients with at least three

grading episodes with fully graded images

of both eyes; and the first two

episodes with no referable diabetic retinopathy (NR = R0 or R1)

Grading protocols differed slightly across the screening centers

Referable retinopathy = moderate nonproliferative diabetic retinopathy (NPDR; equivalent to R2), severe NPDR, or PDR proliferative retinopathy (ETDRS >= 61) in all centers.

Referable maculopathy definitions varied between England and Scotland

Referable diabetic eye disease = composite term for referable retinopathy and referable maculopathy combined

Eyes disease requiring immediate treatment = “treatable diabetic eye disease” and comprised patients with PDR

Yearly (‘invited for annual screening’)

median number of screening episodes

per person included was five

(i.e., two baseline episodes and three

follow-up episodes)

Patients with mild background

Retinop (R1) managed

as R0: receive annual screening

median duration of diabetes

varied from 2-4 years

Risk of progression to STDR is significantly higher for those with background

DR in two consecutive screens

Followup 1.6-3.3

years after the two ‘baseline screenings’

Progression to STDR during followup:

16,196 cases of referable retinopathy (on total of 354,549 patients)

9 risk categories defined at 2^nd baseline screening (cf. Stratton 2013; but note difference in sequence);

main categories:

Level-1

High risk

R1R1/R1R1 (equivalent)

N=20,244 (5.7%)

Mean fup=1.6-2.8

Refer disease by 1, 2, 3, 4 years:

8-15%

13-29%

16-41%

21-46%

Level-5

Medium risk

R1R0/R1R0

(equivalent)

N=16,679 (4.7%)

Mean fup=1.6-3.1

Refer disease by 1, 2, 3, 4 years:

0.9-5.0%

1.5-9.1%

3.7-13.9%

5.5-17.7%

Level-9

Low risk

R0R0/R0R0

(equivalent)

N=242,475 (68%)

Mean fup=2.2-3.3

Refer disease by 1, 2, 3, 4 years:

0.1-0.5%

0.3-1.3%

0.4-2.4%

0.6-3.6%

[see paper for expected progression to proliferative retinopathy]

No formal

testing/

implicit

It may be possible to stratify patients for risk, according to baseline retinal criteria, into groups with low and high risk of their conditions progressing to proliferative

retinopathy.

‘By reducing the screening interval to

2 years for low-risk groups, and increasing

it to every 6 months for high-risk groups, there would be a reduction of

14–40% in screening episodes across the seven screening programs’

Type 1 and 2: not analyzed separately; majority Type 2

Largest study to date

Of patients with no retinopathy in

either eye for two successive screening episodes at least 12 months apart, the

conditions of between 0.3% (95% CI 0.0–0.8%) and 1.3% (1.0–1.6%) of patients progressed to referable retinopathy, and rates of treatable eye disease [= PDR] were <0.3% at 2 years. The corresponding progression rates for patients with bilateral

background retinopathy in successive screening episodes were 13–29% and up to 4%, respectively, in the seven different programs.

Note: low-risk group of patients accounts

for between one-half and two-thirds of patients within the U.K. retinal screening populations

Note: heterogeneity among the seven U.K. centers is important

finding, and may reflect differences in age, sex, and ethnicity profiles, glycemic and blood

pressure control, screening protocols, screening uptake, completeness of

screening register, and the use of exclusion

criteria. However, the variability may also reflect differences in grading.

‘Standardization

of grading protocols and quality assurance may reduce the variation currently observed among centers.’

Note: risk stratification [based on result of 2 consecutive screens at least 12 months apart]

is useful in the U.K. screening programs because, unlike other risk estimation models proposed, it requires

no clinical or demographic information.

Note: ideal study would be RCT, but >120,000 patients would be required which is hardly feasible; ‘smaller scale RCT looking at impact on attendance would be valuable’

Author

and year

publication

Study design/

period (length

of follow-up)

Sample size/

country

(ethnicity)

Age at

diagnosis

or entry in

the screening

programme

Diabetes

type

Setting

Screening

modality

Screening

Frequency compared

Assessment of

screening interval

Authors’

conclusion

about screening

interval

Comments

Davies 1996

[From Echouffo 2013]

Modelling

study

Hypothetical

cohort of

1000/UK

(mostly

Caucasian)

< 35 years

Type 1

diabetes

Populationbased

(primary

care)

Ophthalmoscopy

1 year

2 years

Net benefit of

reducing the

screening interval

from 2 years to

1 year: 0.25 to

0.42 years of sight

saved per person,

depending on

screening methods

used or the screener

(ophthalmologist,

general practitioner

or optometrist)

A 2-year screening

regimen may have

no detrimental effect compared with yearly screening for people with no or mild retinopathy

Relatively old study (before year 2000); because of relatively high incidence of STDR, these studies are less relevant

Liu 2003

[From Echouffo 2013]

Modelling

study

(Markov

modelling)

based on a

date from a

real screening

programme

with 7.4 years

of follow-up

Hypothetical

population of

80,000

/Taiwan

(Chinese)

≥ 40

Type 1

diabetes

and

Type 2

diabetes

Populationbased

Ophthalmoscopy

1 year,

2 years

4 years

Annual screening,

biennial screening

and a 4-yearly

screening regimen

can lead to 54%

(95% CI 44–62%),

51% (95%

CI 41–59%) and

46% (95% CI

36–54%) reductions

in blindness,

respectively

A screening interval of

up to 4 years for patients without diabetic retinopathy

may be justified

Tung 2006

[From Echouffo 2013]

Modelling

study based

on data

from a real

screening

programme

Hypothetical

population

1 000 000/

Taiwan

(Chinese)

≥ 30

Type 2

diabetes

Populationbased

Mydriatic

indirect

ophthalmoscopy

and mydriatic

single-field fundus

photography/

interpreted by two

ophthalmologists

1 year,

2 years,

3 years

4 years

Incidence of blindness

reduction for various

screening regimens:

annual 94.4% (95%

CI 91.6–96.3%);

biennial 83.9% (95%

CI 83.6–84.2%);

3-year 70.2% (95%

CI 69.8–70.7%);

4-year 57.2% (95%

CI 56.7–57.7%);

5-year 45.6% (95%

CI 45.0–46.1%)

Annual screening is the most effective for

reducing incidence of

blindness

Chalk 2012

Modelling

study based

on data

from a real

screening

programme

Hypothetical

cohort of

5000/UK

(mostly

Caucasian)

Not stated, but study is based on NHS screening program (UK)

Type 2

Populationbased

Digital retinal photography

carried out by retinal screening

graders; secondary retinal

grader checks positive results to maximize diagnostic

accuracy (sens and spec are 98.9 and 99.5% resp)

1 year (R0 and R1)

2 years (R0 = no DRP)

In both scenarios, R1 (background DRP) is screened annually, and R2 (pre-proliferative DRP) every 6 months

Based on comparative 15-year forecasts, predicted vision loss is 1.9% (± 0.1 SD) and is identical under both scenarios

Screening people with type 2 diabetes, who have not yet developed retinopathy (R0),

every 2 years, rather than annually, is a safe and cost-effective strategy; does not increase risk of

vision loss (and reduces number of visits for patients w/o DRP with 47%; could reduce screening costs by 25%)

86% likeliness to attend screening appointment; patients in model started 55%R0, 38%R1, 4.9%R2 and 2.6%R3 (taken from the NHS data); probabilities of progression based on Melbourne cohort study (prob over 5 years: R0-R1 0.096; R1-R2 0.187; R2-R3 0.25; R2-vision loss 0.22)

Results are sensitive to the progression rates used for retinopathy (but rates used are similar to those in literature)

Authors stress the importance of retinal clinicians using discretion on a case-by-case basis; more frequent screeing may be prudent for some patients due to increased risk (individual risk factors)

Day 2014

Modelling

study based

on data

from a real

screening

programme

simulated RCT with 5000 agents (‘patients’) using agent-based / discrete event

simulation based on abstracted data from

retrospective cohort of real-world diabetic Veterans (501 patients)

Average age 66.6 years

US veterans: 98% male; average bmi 31.9

Tertiary care facility for 55,000 Veterans

Not stated (likely majority type 2)

Population in tertiairy care: elderly US veterans

Not specified

1 year

2 years

3 years

4 years

5 years

Vision loss among 5000 veterans with background DRP at baseline in 10 year period, as a function of screening duration:

1 year 60.38(SD5.26)

2 year 60.42(7.66)

3 year 65.36(7.99)

4 year, 67.12(8.30)

5 year, 67.88(7.65)

statistics: 1 vs 2 year (not significant); 1 vs 3 years (p<0.01); 2 vs 3 years (p=0.011)

Increasing the screening interval for diabetic patients with background DRP from 1 to 2 years appears safe, while increasing the interval to 3 years heightens risk for vision loss

novel application of simulation architecture combining discrete event simulation (DES)

and agent-basedmodeling (ABM): pilot study; predictors of DRP and the probability of progression from background DRP to proliferative DRP are determined using a veterans data set (501 patients); validity of results is limited by the veteran data used (specific population; single clinic), and simplifications in the clinical model; not clear how progression from R0 (no DRP) to R1 (background DRP) is taken into account

Looker 2013

 Modelling study

(Markov

modelling)

based on a

date from a

real screening

programme

2005-2011

Hidden Markov models to calculate probabilities of transitions to referable DRP (referable background or proliferative retinopathy) or referable maculopathy.

155,114 with no referable DRP or maculopathy at baseline: 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative

retinopathy).

median number [IQR]

examinations = 4 [3-5]

median interval =

12.7 months [12.1–13.9]

≥ 12

Type 1

diabetes

and

Type 2

diabetes

Populationbased

Scottish Diabetic Retinopathy Screening (DRS) programme data 2005-2011

155,114 patients:

139034 type 2 (90%); 16080 type 1 (10%)

Retinal photography

1 year

2 year

Observed transition rates to referable DRP (referable background or proliferative retinopathy) or referable maculopathy (‘any referable disease’) in 2005-2011:

no visible retinopathy vs mild background retinopathy at prior examination: any referable disease 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2

Probability of referable disease (Markov model):

2 consecutive screens showing no visible retinopathy: referable DRP <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years; ; any referable disease <1.2% for type 1 and <0.9% for type 2 at 2 years.

>20% of individuals with observable retinopathy or maculopathy transition to any referable disease at next examination (type 1 and type 2 diabetes)

type 2 diabetes and 2 consecutive screens showing no visible retinopathy, have lowest transition rate

Lowest transition rate for patients with type 2 diabetes and 2 consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009 (using a less stringent rule of having only the last screening finding of no visible retinopathy, this percentage would be 63%)

Individuals with

type 2 diabetes and no visible retinopathy at their last screening

have a low risk of developing referable retinopathy within

a 1 year (≤0.06%) or 2 year screening interval (≤0.22%). If two consecutive screenings showed no visible retinopathy, the risks were even lower (≤0.03% after a 1 year interval and

≤0.15% after a 2 year interval even with a diabetes duration of

15 years).

Risk factors: transition to referable disease

in a 2 year interval was higher in those with longer duration of type 2 diabetes and in those with type 1 diabetes.

Striking amount

of regression, particularly at lower degrees of retinopathy: 18.2% with type 1 diabetes and 36.4% with type 2 transitioned from mild

background retinopathy to no visible retinopathy at their subsequent examination.

Hidden Markov model allows for modelling progression as well as regression; largest data set on screening available to date;

risk of progression at any given duration and retinopathy grade was also consistently higher for people with type 1 diabetes than for people with type 2 diabetes For type 1 diabetes, the effect of duration was marked for up to 10 years, after which duration had little effect on risk estimates.

Use of additional covariate data could allow us to determine more ‘personalised’ screening intervals

Note: rates at 2 years

are higher than at annual screening and alteration in screening interval will ultimately require consideration of

the ‘acceptable’ absolute rate of interval disease, especially for proliferative retinopathy, as well as other factors such as

cost–benefits. In particular we should consider the possible

impact of reduced clinical contact and opportunities to use detection of non-referable retinopathy and maculopathy for improving overall diabetic control.

Van der Heijden 2014

Validation study for personalised screening model based on based on

diabetes-related risk factors (Aspelund 2011)

model calculating a personalised screening interval

for monitoring retinopathy based on patients’ risk profile

Validated using data of 3,319 type 2 diabetic patients

in Diabetes Care System West-Friesland, NL, between 1998-2010

> 60 (mean)

Type 2 diabetes

Populationbased

Diabetes Care System (DCS) West-Friesland, NL

3,319 type 2 diabetes patients

Patients w/o graded photographs, patients with STR at baseline, patients w/o graded fundus photograph within 1 year after model-based time of screening, were excluded >> 3,319 in study sample

Fundus photography (EURODIAB classification)

0= no DRP

1= minimal

2= mod non-prolif

3= sev non-prolif

4= photocoag DRP

5= prolif DRP

3-5= defined as STR, sight-threatening retinopathy

Personalized screening interval (according to model)

Model calculation:

mean screening interval of 31 months;

74% were assigned a

screening interval > 12 months and 53% a screening interval >

24 months

During 53 months follow-up, 76 patients (2.3%) developed STR. Using the model, the mean screening interval was 31 months = reduced screening frequency of 61% compared with annual and 23% compared with biennial screening.

STR incidence occurred after mean 26 months after model-based time of screening in 67 patients (88.2%).

In nine patients (11.8%), STR had developed before model-based time of screening.

A large reduction in retinopathy screening was achieved using the model in this population of

patients with a very low incidence of retinopathy.

Considering the number of potentially missed cases of STR, there is room for improvement in the model.

Use of the model for

Personalised screening may eventually help to reduce healthcare use and costs of diabetes care.

First study to validate the model for personalised

screening of diabetic retinopathy of Aspelund (2011); the model overestimates the risk of developing grades 3–5 retinopathy; study cohort consists of a well-treated group of type 2 diabetic patients, in whom glucose and blood pressure control are very well maintained

Note: A limitation of personalised screening is that it is dependent on the accuracy and punctuality of the care system and care professionals.